全文获取类型
收费全文 | 3383篇 |
免费 | 210篇 |
国内免费 | 5篇 |
出版年
2023年 | 6篇 |
2022年 | 19篇 |
2021年 | 46篇 |
2020年 | 21篇 |
2019年 | 27篇 |
2018年 | 44篇 |
2017年 | 27篇 |
2016年 | 55篇 |
2015年 | 122篇 |
2014年 | 155篇 |
2013年 | 201篇 |
2012年 | 237篇 |
2011年 | 234篇 |
2010年 | 156篇 |
2009年 | 162篇 |
2008年 | 218篇 |
2007年 | 238篇 |
2006年 | 223篇 |
2005年 | 259篇 |
2004年 | 221篇 |
2003年 | 187篇 |
2002年 | 190篇 |
2001年 | 26篇 |
2000年 | 21篇 |
1999年 | 49篇 |
1998年 | 56篇 |
1997年 | 34篇 |
1996年 | 35篇 |
1995年 | 38篇 |
1994年 | 41篇 |
1993年 | 24篇 |
1992年 | 20篇 |
1991年 | 22篇 |
1990年 | 24篇 |
1989年 | 15篇 |
1988年 | 18篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 15篇 |
1984年 | 15篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 23篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1973年 | 3篇 |
排序方式: 共有3598条查询结果,搜索用时 15 毫秒
151.
Amphiphilic vinyl polymers (in the free and cross-linked forms), carrying carboxyl and imidazole groups, were prepared by a radical polymerization of the purposely synthesized N-acryloyl-L-histidine. The protonation thermodynamic studies (at 25 degrees C in 0.15 M NaCl) showed high polyelectrolyte character of the soluble polymer. Unlike the linear decreasing trend of the basicity constant, over the whole range of alpha (degree of protonation), the enthalpy changes for the protonation of the imidazole nitrogen in the polymer showed a decreasing pattern only at alpha > 0.5. This was ascribed to the formation of hydrogen bonds between protonated and free neighboring monomer units. Viscometric data revealed a minimum hydrodynamic volume of the polymer at its isoelectric point (pH 5), whereas at higher or lower pHs, the macromolecule expanded greatly as a consequence of the charged sites formation. This produced a preferential solvation of the protonated imidazole and carboxylate ions, the latter being surrounded by more water molecules in the hydration shell. The peculiar hydration behavior was confirmed in the cross-linked polymer. The hydrogel showed an equilibrium degree of swelling (EDS), strongly dependent on pH, in a similar manner as viscometric data of the soluble polymer. A linear relationship between the reduced viscosity and the EDS was found. The polymer was non toxic against the RAW264 cell line. 相似文献
152.
Poly[(R)-3-hydroxybutyrate] (PHB) depolymerases adsorbed on poly(L-lactide) (PLLA) thin film were directly observed by atomic force microscopy (AFM). A PLLA thin film of 100 nm thickness was prepared on a silicon wafer by spin-cast method. The PLLA thin film was treated at 220 degrees C and quenched to room temperature, resulting in the formation of a completely amorphous film with a smooth surface. Then, the PHB depolymerases from Pseudomonas stutzeri YM1006 and Ralstonia pickettii T1 were dispersed on the amorphous PLLA thin film. Direct AFM observation has revealed that the PHB depolymerases bind in an elliptic shape on the surface of the PLLA thin film and that a small ridge is created around each enzyme molecule. After removal of the enzymes with 40% ethanol aqueous solution, small hollows were found on the PLLA thin film. These results suggest that a PHB depolymerase interacts with polyester molecules during their adsorption to make a hollow on the substrate surface. 相似文献
153.
Yoshizumi T Takahashi H Ohtake N Jona H Sato Y Kishino H Sakamoto T Ozaki S Takahashi H Shibata Y Ishii Y Saito M Okada M Hayama T Nishikibe M 《Bioorganic & medicinal chemistry》2004,12(9):2139-2150
The synthesis and structure-activity relationships of a series of 5,7-diarylcyclopenteno[1,2-b]pyridine-6-carboxylic acids are described. Our efforts have been focused on modification of the aryl ring at the 5-position and the alkyl substituent at the 2-position of the bottom 4-methoxyphenyl ring in an effort to develop orally available ET(A) selective antagonists with safer profiles in terms of the P-450 enzyme inhibitory activity. Incorporation of a hydroxymethyl group as an alkyl substituent in methylenedioxyphenyl and 6-dihydrobenzofuran derivatives led to the identification of orally bioavailable ET(A) selective antagonists 1f and 7f. These compounds also showed not only excellent binding affinity (IC(50) < 0.10nM, more than 800-fold selectivity for the ET(A) receptor over the ET(B) receptor) but also sufficient oral bioavailability, 48% and 56%, respectively, in rats. Furthermore, these compounds did not exhibit either competitive or mechanism-based inhibition of human cytochrome P450 enzymes. 相似文献
154.
Tanitame A Oyamada Y Ofuji K Fujimoto M Suzuki K Ueda T Terauchi H Kawasaki M Nagai K Wachi M Yamagishi J 《Bioorganic & medicinal chemistry》2004,12(21):5515-5524
The 4-piperidyl moiety and the pyrazole ring in 1-(3-chlorophenyl)-5-(4-phenoxyphenyl)-3-(4-piperidyl)pyrazole 2, which has previously shown improved DNA gyrase inhibition and target-related antibacterial activity, were transformed to other groups and the in vitro antibacterial activity of the synthesized compounds was evaluated. The selected pyrazole, oxazole and imidazole derivatives showed moderate inhibition against DNA gyrase and topoisomerase IV with similar IC(50) values (IC(50)=9.4-25 microg/mL). In addition, many of the pyrazole, oxazole and imidazole derivatives synthesized in this study exhibited potent antibacterial activity against quinolone-resistant clinical isolates and coumarin-resistant laboratory isolates of Gram-positive bacteria with minimal inhibitory concentration values equivalent to those against susceptible strains. 相似文献
155.
Xu WP Shiba H Mizuno N Uchida Y Mouri Y Kawaguchi H Kurihara H 《Cell biology international》2004,28(10):675-682
Bone morphogenetic proteins (BMPs) have multiple functions in the development and growth of skeletal and extraskeletal tissues. Therefore, BMPs may regulate the regeneration of periodontal tissue. To investigate this issue, we examined the effects of BMP-4, -5 and -6 on DNA synthesis and the expression of bone-related proteins in cultures of human periodontal ligament (HPL) cells. The expression of bone-related proteins was determined by Real-time polymerase chain reaction and enzyme linked immunosorbent assay in cultures of HPL cells. DNA synthesis was estimated by measuring bromoderoxyuridine incorporation. It was found that BMP-4, -5 and -6 enhanced DNA synthesis dose-dependently. BMP-4 and -5 increased the levels of osteopontin, BMP-2, alkaline phosphatase and core binding factor alpha 1 mRNAs. BMP-6 stimulated the expression of osteopontin, BMP-2, ALPase and osteoprotegerin. These findings show that BMP-4, -5 and -6 have different actions on the expression of bone-related proteins and may play a role in the regeneration of periodontal tissue by promoting cell proliferation and protein expression. 相似文献
156.
Characterization of the chromosomal binding sites and dimerization partners of the viral oncoprotein Meq in Marek's disease virus-transformed T cells 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Levy AM Izumiya Y Brunovskis P Xia L Parcells MS Reddy SM Lee L Chen HW Kung HJ 《Journal of virology》2003,77(23):12841-12851
157.
Ebola virus budding is mediated by two proline-rich motifs, PPxY and PTAP, within the viral matrix protein VP40. We have previously shown that a Nedd4-like protein BUL1, but not Nedd4, positively regulates budding of type D retrovirus Mason-Pfizer monkey virus (J. Yasuda, E. Hunter, M. Nakao, and H. Shida, EMBO Rep. 3:636-640, 2002). Here, we report that the cellular E3 ubiquitin ligase Nedd4 regulates budding of VP40-induced virus-like particles (VLPs) through interaction with the PPxY motif. Mutation of the active site cysteine (C894A), resulting in abrogation of ubiquitin ligase activity, impaired the function of Nedd4 on budding. In addition, the WW domains of Nedd4 are essential for binding to the viral PPxY motif, and a small fragment of Nedd4 containing only WW domains significantly inhibited Ebola VLP budding in a dominant-negative manner. Our findings suggest that the viruses containing PPxY as an L-domain motif specifically use E3 in the process of virus budding. We also examined the effects of overexpression of Tsg101 and its mutant. As expected, Tsg101 enhanced VP40-induced VLP release, and TsgDeltaC, which lacks its C-terminal half, inhibited VLP release. These results indicate that Nedd4, together with Tsg101, plays an important role in Ebola virus budding. 相似文献
158.
159.
Takada A Feldmann H Stroeher U Bray M Watanabe S Ito H McGregor M Kawaoka Y 《Journal of virology》2003,77(2):1069-1074
Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. Passive transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L. Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes responsible for neutralization have been only partially characterized because some of the MAbs do not recognize the short synthetic peptides used for epitope mapping. To identify the amino acids recognized by neutralizing and protective antibodies, we generated a recombinant vesicular stomatitis virus (VSV) containing the Ebola virus glycoprotein-encoding gene instead of the VSV G protein-encoding gene and used it to select escape variants by growing it in the presence of a MAb (133/3.16 or 226/8.1) that neutralizes the infectivity of the virus. All three variants selected by MAb 133/3.16 contained a single amino acid substitution at amino acid position 549 in the GP2 subunit. By contrast, MAb 226/8.1 selected three different variants containing substitutions at positions 134, 194, and 199 in the GP1 subunit, suggesting that this antibody recognized a conformational epitope. Passive transfer of each of these MAbs completely protected mice from a lethal Ebola virus infection. These data indicate that neutralizing antibody cocktails for passive prophylaxis and therapy of Ebola hemorrhagic fever can reduce the possibility of the emergence of antigenic variants in infected individuals. 相似文献
160.